Our People » Prof Warren Tate
My laboratory has had a long-term interest in understanding protein synthesis and, in particular, decoding and recoding mechanisms on the ribosome at stop signals. Important recent investigations have focused on how the decoding release factor as a molecular mimic of tRNA recognises the individual bases of the stop signal, and how alternative genetic codes like those found in vertebrate mitochondria can be accommodated into an integrated model. This has been helped considerably by the 2008 atomic resolution structures of the ribosome:factor complex.
The decoding release factor interacting
From our chance discovery in the 1980s of recoding (frameshifting; a cellular mechanism for regulating gene expression during protein synthesis), we developed an interest in the frameshift mechanism of HIV-1 as a potential site of vulnerability in the virus. Now, our interest has extended to the only gene in the animal kingdom known to use this mechanism, human gene PEG10. The gene was relatively recently acquired as a retroelement insertion and has undergone molecular domestication to become expressed in placenta and amniotic membranes but not, as we have shown, in adult tissues. Significantly, it uses the same frameshifting expression strategy as HIV-1 to produce two proteins.
Morris water maze: testing memory in a rat
A second long-standing interest has been the molecular mechanisms of mammalian memory and how they are impaired in human neurological diseases, particularly Alzheimer’s. These investigations have focused on the molecular changes in neurons of the hippocampus when they receive electrical signals within in vivo models and more recently included behavioural studies. We have developed a simple recombinant production and purification strategy for a processed brain protein, secreted amyloid precursor protein-alpha, a protein that is neuroprotective but whose concentration is lowered in Alzheimer’s patients. Remarkably, we have shown our recombinant protein alone can restore memory to rats impaired by drug treatment, not only in their electrophysiological responses but also in trials to determine memory of learned spatial tasks. We believe this external secreted protein is a signalling molecule that can switch on a signalling pathway and activate a range of gene responses to protect and enhance memory; an activity that may be critical as a counterbalance in the development of Alzheimer’s disease.
Health Research Council of New Zealand
S. Baratchi, J. Evans, W P Tate, W C Abraham, and B. Connor, Secreted amyloid precursor proteins promote proliferation and glial differentiation of adult hippocampal neural progenitor cells, Hippocampus 2012 vol. 22 (7) pp. 1517-1527, Link »
Harold S Bernhardt and Warren P Tate, Primordial soup or vinaigrette: did the RNA world evolve at acidic pH?, Biology direct 2012 vol. 7 p. 4, Link »
Jacobs, G.H., Chen, A., Stevens, S.G., Stockwell, P.A., Black, M.A., Tate, W.P., Brown, C.M. Transterm: a database to aid the analysis of regulatory sequences n mRNAs. Nucleic Acids Research 37: D72-D76 (2009)
Bernhardt, H.S., Tate, W.P. Evidence from glycine transfer RNA of a frozen accident at the dawn of the genetic code. Biology Direct 3: 53 (2008)
Taylor C.J, Ireland, D.R., Ballagh, I., Bourne, K., Turner, P., Tate, W.P., and Abraham, W.C. Endogenously secreted amyloid precursor protein-alpha regulates hippocampal NMDA receptor function, long-term potentiation and spatial memory. Neurobiology of Disease 31:250-260 (2008)
Clark, M., Jänicke, M., Gottesburen, U., Kleffmann, T., Legge, M., Poole, E., Tate, W. Mammalian gene PEG10 expresses two reading frames by high efficiency –1 frameshifting in embryonic-associated tissues. Journal of Biological Chemistry 282:37359-37369 (2007)
Williams, J.M., Guevremont, D., Mason-Parker S.E., Luxmanan, C., Tate W.P., Abraham, W.C. Differential trafficking of AMPA and NMDA receptors during long-term potentiation in awake adult animals. Journal of Neuroscience 27: 14171-14178 (2007)
Suleimanpour-Lichae R., Kuhl, I., Gaisne, M., Passos J., Wydro ,M., Rorbach, J., Temperley, R., Bonnefoy, N., Tate, W., Lightowlers, R., Chrzanowska-Lightowlers, Z. mtRF1 is a human mitochondrial release factor decoding the major termination codons UAA and UAG. Molecular Cell 27:745-757 (2007)
Turner, P. R, Bourne K., Garama, D, Abraham, W.C., Tate W.P. Production, purification and functional validation of human secreted amyloid precursor proteins as neuropharmacological reagents. Journal of Neuroscience Methods 164:68-74 (2007)
Poole, E.S., Young, D.J., Askarian-Amiri, M.E., Debbie-Jane G. Scarlett, D-J.G., Tate, W.P. Accommodating the bacterial decoding release factor as an alien protein among the RNAs at the active site of the ribosome. Cell Research 17:591-607 (2007)
Cridge, A.G., Major, L.L., Mahagaonkar, A.A., Poole, E.S., Isaksson, L.A., Tate, W.P. Comparison of characteristics and function of translation termination signals between and within prokaryotic and eukaryotic organisms. Nucleic Acids Research 34:1959-1973 (2006)
Jacobs, G.H., Stockwell, P.A., Tate, W.P., Brown, C.M. Transterm – extended search facilities and improved integration with other databases. Nucleic Acids Res 34: D37-D40 (2006)